Most bacterial pathogenesis studies have focused on mono-culture infections; however it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization and persistence in the infection site. Such interactions have been particularly noted in wound infections, although the molecular processes controlling these synergistic interactions are generally not known. Detailed mechanistic studies of the polymicrobial interactions required for enhanced persistence in vivo are a necessary first step towards developing therapeutics to treat polymicrobial infections. The overall goal of this research plan is to determine how interactions between Pseudomonas aeruginosa and other microbes that commonly co-infect wounds impact wound severity. To accomplish this goal, in vivo murine wound models and high-throughput genomics techniques will be employed to identify and characterize microbial genes required for enhanced pathogenesis during co-infection.